392TiP - A prospective phase II study of individualized adjuvant therapy in patients with locally advanced hypopharyngeal cancer after neoadjuvant therapy

Background

Hypopharyngeal cancer is relatively rare, accounting for only 3% of head and neck cancers. A majority of the patients (pts) present at an advanced stage with a 5-year overall survival of 40%. Despite improvement in local regional control with neoadjuvant therapy, distant metastasis led to poor outcomes in hypopharyngeal cancer. Individualized adjuvant therapy based on pathologic complete response (pCR) and CD8+ T cell infiltration may be a promising strategy for pts after neoadjuvant therapy. Thus, we conducted a phase II study (ChiCTR2200055939) to evaluate the efficacy and safety of neoadjuvant and individualized adjuvant therapy and explore the correlation between tertiary lymphoid structures (TLS) and efficacy/immune microenvironment in pts with locally advanced hypopharyngeal cancer.

Trial design

In the prospective, open-label, single-arm phase II study, pts who have histologically or cytologically confirmed stage II-IVa hypopharyngeal cancer without recurrent/metastatic disease, ECOG performance status of 0-1, and predicted survival >3 months are eligible. Pts will intravenously receive 2-cycle neoadjuvant therapy with pembrolizumab (200 mg), albumin-bound paclitaxel (260 mg/m2), and cisplatin (100 mg/m2) on day 1 every 3 weeks. Surgical resection will be scheduled within 21-28 days after the final dose of neoadjuvant therapy. If postoperative pathology shows a pCR, pembrolizumab will be given as adjuvant therapy for 15 cycles. Pts with non-pCR but CD8+ cell density increased ≥20% from baseline will receive adjuvant radiotherapy (50-60Gy) plus pembrolizumab for 15 cycles; otherwise, non-pCR pts will withdraw from the study and receive conventional concurrent chemoradiotherapy. The primary endpoint is 12-month recurrence-free survival (RFS). Secondary endpoints are 18- and 24-month RFS, median RFS, pCR rate, and safety. Exploratory endpoints include the correlation between TLS and pathological response/RFS/immune microenvironment (eg, CD8+ cells, B/T lymphocytes). The phase 2 trial is ongoing.

Clinical trial identification

ChiCTR220005593p.

Legal entity responsible for the study

The Sixth Medical Center of Chinese PLA General Hospital.

Funding

Wu Jieping Medical Foundation.

Disclosure

All authors have declared no conflicts of interest.